Background: : In this experiment, we intend to investigate the relationship between ER alpha 36 expression and endometrial cancer. Materials and Method: A total of 172 healthy control and endometriosis patients were selected from our hospital. These included 43 cases of normal endometrium (NE group), 43 cases of endometrium without atypical hyperplasia (EH group), 43 cases of atypical hyperplasia (AH group) and 43 cases of endometrial cancer (EC group). The expression of ER-alpha 36 in these tissues was detected by immunohistochemical methods. Results: The positive rate of estrogen receptor (ER-alpha 36) in each group was 4.24%+/- 5.02%, 5.74%+/- 6.34%, 9.69%+/- 9.42%, and 11.78%+/- 10.39%, respectively. The expression of ER-alpha 36 demonstrated a notably higher level in the AH and EC groups compared to the EH and NE groups. A statistically significant difference was observed between the NE group and the AH group (P=0.0112). The NE group was statistically different from the EC group (P=0.0001).There was a statistical difference between the EH group and the EC group (P=0.0040). Among endometrial cancers, the mean positive rate of ER-alpha 36 expression was 11.67%+/- 6.74% in highly differentiated endometrial cancers, 9.45%+/- 11.38% in moderately differentiated, and 14.82%+/- 11.35% in poorly differentiated. Comparison between the two groups showed that there was no statistically significant difference in the expression positivity rate of ER-alpha 36 in endometrial cancer of different degrees of differentiation (P>0.05). Conclusion: ER-alpha 36 has a certain diagnostic efficacy for endometrial cancer and can be used as an auxiliary judgment tool for pathological examination.